Exosomal miR‐181d‐5p Derived from Rapamycin‐Conditioned MDSC Alleviated Allograft Rejection by Targeting KLF6

作者：Chao Wei, Yaru Sun, Fanxing Zeng, Xiunian Chen, Li Ma, Xiaoxue Liu, Xiaolin Qi, Weiyun Shi, Hua Gao · 发表于：Advanced Science · 年份：2023 · DOI：10.1002/advs.202304922 · 被引用次数：23 · 研究领域：Extracellular vesicles in disease、Reproductive System and Pregnancy、MicroRNA in disease regulation

Immune rejection and side effects of long-term administration of immunosuppressants are the two major obstacles to allograft acceptance and tolerance. The immunosuppressive extracellular vesicles (EVs)-based approach has been proven to be effective in treating autoimmune/inflammatory disorders. Herein, the anti-rejection advantage of exosomes (Rapa-Exo) from rapamycin-conditioned myeloid-derived suppressor cells (MDSCs) over exosomes (Exo-Nor) from the untreated MDSCs is shown. The exosomal small RNA sequencing and loss-of-function assays reveal that the anti-rejection effect of Rapa-Exo functionally relies on miR-181d-5p. Through target prediction and double-luciferase reporter assay, Kruppel-like factor (KLF) 6 is identified as a direct target of miR-181d-5p. Finally, KLF6 knockdown markedly resolves inflammation and prolongs the survival of corneal allografts. Taken together, these findings support that Rapa-Exo executes an anti-rejection effect, highlighting the immunosuppressive EVs-based treatment as a promising approach in organ transplantation.